Homocysteine, a three carbon sulfidhydral amino acid, (Cys C), CAS Registry Number 52-90-4, having the molecular formula C.sub.3 H.sub.7 NO.sub.2 S [HS--CH2--CH(NH2)--COOH] and a molecular weight of 121.15, has attracted interest because of its relationship to the development of cardiovascular disease. Numerous studies have shown that patients with myocardial infarction, stroke, or peripheral occlusive arterial disease are frequently hyperhomocysteinamic.
This literature includes:
Clarke, R., et al. Hyperhomocysteinemia: An Independent Risk Factor for Vascular Disease. The New England Journal of Medicine, 1991, 324:1149-1155.
Stamfer, M. J., et al. A Positive Study of Plasma Homocyst(e)ine and Risk of Myocardial Infarction in U.S. Patents. JAMA, 1992, 268:877-881.
Malinow, M. R. Homocyst(e)ine and arterial occlusive diseases. Journal of Internal Medicine, 1994, 236:603-617.
Brattstrom, L., et al. Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. Journal of Internal Medicine, 1994, 236:633-641.
Arnesen, E., et al. Serum Total Homocysteine and Coronary Heat Disease. International Journal of Epidemiology, 1995, 24:704-709.
Selhub, J., et al. Association Between Plasma Homocysteine Concentrations And Extracranial Carotid-Artery Stenosis. The New England Journal of Medicine, 1995, 332:286-291.
Perry, I. J., et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet, 1995, 346:1395-1398.
Boushey, C. J., et al. A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease. JAMA, 1995, 274:1049-1057.
McCulley, K. S. Homocysteine, Foliate, Vitamin B.sub.6, and Cardiovascular Disease. JAMA, 1996, 279:392-393.
Verhoef, P., et al. Homocysteine Metabolism and Risk of Myocardial Infarction: Risk with Vitamins B.sub.6, B.sub.12 and Foliate. American Journal of Epidemiology, 1996, 143:845-859.
Cowley, G. The Heart Attackers. Newsweek, Aug. 11, 1997, 54-60.
Rosenberg, I. H., et al. Colloquium: Homocyst(e)ine, Vitamins and Arterial Occlusive Diseases. American Institute of Nutrition. J. Nutr., 1996, 126:1235S-1300S.
Graham, I. M., et al. Plasma Homocysteine as a Risk Factor for Vascular Disease. JAMA, 1997, 277:1775-1791.
It has been reported that an elevated plasma concentration of homocysteine increases the risk for coronary, peripheral and cerebral vascular diseases. It is now known that mild hyperhomocysteinemia is a risk factor independent of cholesterol, smoking status, and systolic blood pressure for cardiovascular disease, thrombotic events and atherosclerosis.
Quite recently, both of two prospective studies, the U.S. Physicians' Study and the Tromoso Study, showed hyperhomocysteinemia to be an independent risk factor for myocardial infarction. Ueland et al. showed that fasting plasma concentration of homocysteine in vascular disease patients was 31% higher than normal subjects. Similarly, in the Physicians' Health Study, Stampfer et al observed that men with myocardial infarction had a higher plasma homocysteine concentration than those free of infarction. More strikingly, they found that even a small increase in plasma homocysteine concentration (i.e., 1.7 mol/L or 12% above the upper limit of normal range) increased the risk for acute myocardial infarction by more than three-fold. The most recent epidemiological study by Selhub et al. demonstrated that the odd ratio for carotid-artery stenosis of greater than 25% was 2.0 for subjects with homocysteine of 14.4 mol/L as compared to those with 9.1 mol/L. Interestingly, the study revealed that the prevalence of stenosis is inversely related to plasma concentrations of homocysteine in linear fashion.
It has been hypothesized that homocysteine may 1) act as a thrombogenic agent, 2) impair the production of enthothelium-derived relaxing factor, and 3) stimulate proliferation of smooth cells, a key component in atherogenisis.
Garlic preparations are known to possess many beneficial effects in maintaining good health conditions, such as resistance against infections, lowering cholesterol levels, detoxifying harmful substances, relieving stress and enhancing the immune response. One such commercially available product is KYOLIC.RTM., available from Wakunaga of America Co., Ltd., a subsidiary of Wakunaga Pharmaceutical Co., Ltd., and containing Aged Garlic Extract.TM.. However, garlic products, including KYOLIC.RTM., have never been reported to exhibit the beneficial effect on the serum homocysteine levels.
As cardiovascular disease is a prominent cause of death in industrialized countries, any factor which may affect the plasma homocysteine concentration is of great importance to public health. Although the screening of the effective materials to reduce plasma homocysteine level without any adverse effects has been continuously and actively searched, true effective materials have not been discovered yet. There have been no published reports on plant materials such as the family of Liliaceae, genus of Allium.
It is thus an object to provide an improved method and composition for oral administration to mammals (humans) which reduces the concentration of serum homocysteine.
Another object of this invention is the provision of an improved novel method of reducing the concentration of serum homocysteine in mammals by the oral administration of Allium or extracts of Allium in an acceptable pharmaceutically acceptable carrier and in a therapeutic amount.
Yet another object of this invention is to provide an improved and novel product for reducing the concentration of serum homocysteine in mammals by the oral administration of Allium or extracts of Allium in combination with vitamin B.sub.12, vitamin B.sub.6 and folic acid in an acceptable pharmaceutically acceptable carrier and in a therapeutic amount.